We plan to examine three predisposing elements in the behavioral effects of CNS drugs. The first is the strength of environmental stimulus control of behavior. Stimuli--primarily visual--will be precisely specified and then manipulated to determine how changes in behavior produced by drugs are modified by changes in stimulus parameters. Ancillary experiments will determine the degree to which drug-induced impairment of sensory function can account for these results. The second predisposing factor encompases the degree of regulation and restriction exerted by environmental variables other than sensory stimuli; e.g., nature and extent of prior conditioning history and current schedule. Together, the above two predisposing factors represent what we consider to be the major behavioral variables that influence sensitivity to drugs. The third predisposing factor is prior exposure to low levels of drugs and environmental chemicals. Long-term, low-level exposures represent models of toxic processes central to psychopharmacology. Such exposures may shift neurochemical balances in a way that may be revealed primarily in an altered behavioral response to drugs. The primary efforts will be directed towards chronic administration of neuroleptics, with haloperidol serving as the model drug, and an emphasis on movement disorders. We will attempt to place the above behavioral results in a meaningful biological perspective by conducting ancillary studies of neurochemistry and morphology, whenever possible.